Faculty Bibliography

In recent years it has been established that patients with AD have a relatively specific loss of cerebral cortical and hippocampal cholinergic nerve terminals. This may be a reflection of degeneration of cholinergic neurons originating in the nucleus basalis of Meynert and septum which project to the cortex and hippocampus, respectively. In view of the long-standing association of cholinergic mechanisms with cognitive processes and the recognition of selective cholinergic deficits in AD, therapeutic attempts to enhance CNS cholinergic function have been undertaken in patients with AD. While only limited success with this strategy has been achieved to date, the use of TRH may offer a novel, yet rational, approach to treating AD. This assumption is predicated on the extensive literature documenting unique, facilitatory interactions of this peptide with cholinergic neurons throughout the neuraxis. Furthermore, the same rationale may account for the recently reported therapeutic benefit of TRH in patients with amyotrophic lateral sclerosis, which like AD, is a disease whose symptoms are manifested through a progressive degeneration of a subpopulation of CNS cholinergic neurons

A double-blind placebo-controlled study was conducted in 10 individuals with probable Alzheimer's disease to assess the effects of varying doses of Naltrexone (0, 25, 50 and 100 mg) on cognitive functioning and on plasma cortisol. Each individual participated in four separate sessions at least three days apart. Naltrexone was found to improve performance in only one of the six psychometric tasks employed (Token Test). However, enhancement of Token Test performance was limited to the 25 mg Naltrexone dose and was mainly the result of an improvement on the part of the two most severely impaired patients. In contrast to the previous reports of elevations of plasma cortisol following administration of opiate antagonists to younger, non-demented subjects, Naltrexone administration failed to produce any significant increase in plasma cortisol in Alzheimer's patients

Past studies have implicated proline involvement in the function of memory and learning. A new micromethod has been developed that is suitable for measuring proline accurately in as little as 0.1 ml of CSF. In normal human CSF, the average proline level was found to be consistently about 1.3 microM. In the CSF of patients with Alzheimer's disease and mixed dementias, the levels of proline showed no statistically significant difference from proline levels in the CSF of normal controls. Furthermore, the proline levels in the CSF of the Alzheimer's disease patients did not reflect, consistently, the cognitive deficits or the symptomatic severity of the disease. Proline levels in CSF showed no statistically significant change with the age of individuals tested

A case is reported of a recurrent and treatment-resistant depression with a positive DST in an individual in whom adenocarcinoma of the pancreas was eventually diagnosed. Following excision of the tumor, there was increased therapeutic response to antidepressants and normalization of the DST

Lithium treatment in 9 elderly individuals with Alzheimer's disease led to a marked accentuation of extra-pyramidal symptoms (EPS) in 5 of 6 patients with preexisting EPS. EPS scores significantly correlated with plasma and RBC lithium levels. Lithium treatment had no such effects in the 3 patients without preexisting extrapyramidal symptoms

The authors report a case involving a 65-year-old woman with DSM-III criteria for major unipolar depression in whom the administration of zimelidine, a potent and selective 5-hydroxytryptamine reuptake inhibitor, led to the development of a hypersensitivity reaction characterized by a severe headache, low grade fever, abnormal liver enzymes, and generalized myalgia 10 days after initiation of treatment. The most novel aspect of this hypersensitivity reaction to zimelidine was the development of abnormalities in muscle creatine phosphokinase in conjunction with the myalgia